{"doi":"10.17615/8dsb-2z68","title":"The PZP Domain of AF10 Senses Unmodified H3K27 to Regulate DOT1L-Mediated Methylation of H3K79","abstract":"AF10, a DOT1L cofactor, is required for H3K79 methylation and cooperates with DOT1L in leukemogenesis. However, the molecular mechanism by which AF10 regulates DOT1L-mediated H3K79 methylation is not clear. Here we report that AF10 contains a \"reader\" domain that couples unmodified H3K27 recognition to H3K79 methylation. An AF10 region consisting of a PHD finger-Zn knuckle-PHD finger (PZP) folds into a single module that recognizes amino acids 22-27 of H3, and this interaction is abrogated by H3K27 modification. Structural studies reveal that H3 binding triggers rearrangement of the PZP module to form an H3(22-27)-accommodating channel and that the unmodified H3K27 side chain is encased in a compact hydrogen-bond acceptor-lined cage. In cells, PZP recognition of H3 is required for H3K79 dimethylation, expression of DOT1L-target genes, and proliferation of DOT1L-addicted leukemic cells. Together, our results uncover a pivotal role for H3K27-via readout by the AF10 PZP domain-in regulating the cancer-associated enzyme DOT1L.","journal":"UNC Libraries","year":2020,"id":112126,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":259809,"name":"Aniruddha J. Deshpande","orcid":"0000-0002-5240-9356","position":1,"is_corresponding":false},{"id":79074,"name":"Or Gozani","orcid":"0000-0002-1365-4463","position":2,"is_corresponding":false},{"id":227837,"name":"Benjamin A. García","orcid":"0000-0002-2306-1207","position":3,"is_corresponding":false},{"id":236907,"name":"Scott A. Armstrong","orcid":"0000-0002-9099-4728","position":4,"is_corresponding":false},{"id":71449,"name":"Brian D. Strahl","orcid":"0000-0002-4947-6259","position":5,"is_corresponding":false},{"id":247704,"name":"Simone Sidoli","orcid":"0000-0001-9073-6641","position":6,"is_corresponding":false},{"id":531405,"name":"Ze Yang","orcid":"0000-0003-4312-1454","position":7,"is_corresponding":false},{"id":252278,"name":"Dinshaw J. Patel","orcid":"0000-0002-9779-7778","position":8,"is_corresponding":false},{"id":79075,"name":"Alex W. Wilkinson","orcid":null,"position":9,"is_corresponding":false},{"id":531406,"name":"Shoudeng Chen","orcid":"0000-0002-7634-2141","position":10,"is_corresponding":false},{"id":275708,"name":"Krzysztof Krajewski","orcid":"0000-0001-7159-617X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:13.874980Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}